Therapeutic targets in the brain for overactive bladder: A focus on angiotensin II type 1 receptor

Abstract

Overactive bladder is a condition that affects both men and women, and significantly affects patients' quality of life. Anticholinergics, β3-adrenoceptor agonists, and botulinum toxin are currently being used for treatment. However, several patients do not respond to these medications or discontinue them because of adverse events.Angiotensin II (Ang II) is a neuropeptide produced in both brain and peripheral tissues, and Ang II type 1 (AT1) receptors, which are important regions for the micturition reflex, are widely expressed in the cerebral cortex, paraventricular nucleus, solitary tract nucleus, and periaqueductal gray. Our data showed that cumulative central Ang II administration, even at low doses, shortened the intercontraction interval without affecting the blood pressure or blood catecholamine levels. Additionally, Ang II can enhance the micturition reflex by suppressing the GABAergic nervous system and stimulating the downstream pathway of the AT1 receptor. The peripherally administered AT1 receptor blocker telmisartan inhibited central Ang II-induced facilitation of the micturition reflex. Targeting the central AT1 receptor may be a potential treatment approach for patients with overactive bladder. This review introduces the brain AT1 receptor as a therapeutic target in overactive bladder.

Keywords

• Angiotensin II
• Angiotensin II type 1 receptor
• Bladder
• Brain
• Overactive bladder